[S,S]-ethylenediamine-N,N&#39; -discussinic acid crystal with high bulk density and process for obtaining the same

ABSTRACT

Crystals of [S,S]-ethylenediamine-N,N′-disuccinic acid which have a bulk density of 0.45 to 1.2 g/cm 3 , and a process for obtaining these crystals comprising the steps of adjusting an aqueous solution of an [S,S]-ethylenediamine-N,N′-disuccinic acid metal salt to a temperature of 40 to 80° C. and a pH of 1.9 to 4.5, and cooling the solution to a temperature below 40° C. over a period of 0.2 to 10 hours while supplying a mineral acid so as to maintain the pH at 1.9 to 4.5 to precipitate [S,S]-ethylenediamine-N,N′-disuccinic acid in a high yield.

TECHNICAL FIELD

[0001] The present invention relates to[S,S]-ethylenediamine-N,N′-disuccinic acid crystals having a high bulkdensity and a process for obtaining the crystals in a high yield.[S,S]-ethylenediamine-N,N′-disuccinic acid (hereinafter abbreviated as[S,S]-EDDS) is expected to find use as a biodegradative chelating agentfor a detergent composition, a photographic bleaching agent, anelectroless plating assistant and a peroxide stabilizer, etc.

BACKGROUND ART

[0002] Several methods are known for a preparation of [S,S]-isomers ofethylenediamine-N,N′-disuccinic acid, such as (1) a chemical syntheticmethod in which said isomers are synthesized from L-aspartic acid anddibromoethane in a basic aqueous medium according to Neal and Rose etal. (Inorganic Chemistry, Vol. 7, pp. 2405-2412, 1968), (2) a chemicalsynthetic method in which the isomers are synthesized from L-asparticacid and dibromoethane in the presence of calcium hydroxide according toPatel R. N. et al. (WO95-12570), (3) an enzymatic synthetic method inwhich the isomers are synthesized from fumaric acid and ethylenediamineaccording to Endo et al., and (4) a fermentative methods usingactinomyces according to T. Nishikiori et al. (J. Antibiot. 37, 426-427,1994) and Z. Hans et al. (WO9636725).

[0003] As methods for recovering [S,S]-EDDS, there have been proposed,for example, a method in which an [S,S]-EDDS solution is gradually madeacidic with a concentrated hydrochloric acid till reaching the pH of 3.5and then an objective substance is recovered from the solution accordingto Neal and Rose et al., a method for recovering from a calcium salt of[S,S]-EDDS (WO96-01801) according to Atkinson. Eldon. E. et al., and amethod for recovering from an aqueous solution of [S,S]-EDDS andL-aspartic acid salt according to Atkinson. Eldon. E. et al.(WO96-01802). These proposals relate to techniques for recovering[S,S]-EDDS from an [S,S]-EDDS solution obtained by a chemical synthesisfrom L-aspartic acid and dibromoethane, and these techniques areintended to minimize an uptake of coprecipitates at the time of arecovery and to obtain a precipitate in such an amount that theprecipitate can be easily filtered. Any of these proposals, however, aresilent on how to obtain the crystals of [S,S]-EDDS with a high bulkdensity in a high yield.

[0004] According to experiments by the present inventors, the ordinaryacid-precipitation method for example which comprises adding a mineralacid at a normal temperature or under cooling to a reaction liquid of[S,S]-EDDS obtained by the enzymatic synthetic method (3) as mentionedabove involved problems that precipitated [S,S]-EDDS was extremely highbulky needle crystals, a deterging efficiency was bad, a dryingefficiency of the produced crystals was bad, and a transportationefficiency of the crystals was poor because of their large volume perunit weight.

[0005] In order to solve the above problems, the present inventors havemade extensive studies on crystallization conditions of [S,S]-EDDS suchas a temperature, pH and a period of time at the time of thecrystallization. In result, the present inventors found out theconditions under which columnar crystals having a high bulk density canbe obtained, and quite unexpectedly confirmed that a considerable amountof cyclized products of ethylenediamine-N,N′-disuccinic acid representedby the following structural formulae (1) and (2) etc. were contained ina mother liquor in which formed crystals were removed, and that certaincrystallization conditions promote an intramolecular cyclizationreaction to cause a reduction of a recovery yield of [S,S]-EDDS.

[0006] Accordingly, the purpose of the present invention is to suppressa formation of the cyclized products of [S,S]-EDDS at the time ofcrystallization and simultaneously to solve the various problemsencountered in obtaining the [S,S]-EDDS crystals having a high bulkdensity. Solution of these problems is of vital importance for theindustrial production of the crystals of [S,S]-EDDS.

[0007] Regarding cyclized products of ethylenediamine-N,N′-disuccinicacid, those derived from isomeric mixtures thereof ([R,R]-, [S,S]- and[R,S-/S,R]-mixtures) have been reported by Vasil'ev V. P. et al. (Zh.Neorg. Khim. 34(2), 381-385, 1989) and other researchers. However, therehas been report neither on cyclized products derived from opticallyactive [S,S]-isomers alone nor on a formation of the cyclized productsat the time of crystallization.

DISCLOSURE OF THE INVENTION

[0008] As a result of intensive studies for a solution of the aboveproblems, the present inventors found that it was effective for solvingthe above problems to conduct a crystallization under specified pH,temperature and period of time conditions, and succeeded in completingthe present invention on the basis of this finding.

[0009] Thus, the present invention relates to: (1) crystals of[S,S]-ethylenediamine-N,N′-disuccinic acid having a bulk density of from0.45 to 1.2 g/cm³; (2) a process for obtaining the crystals described in(1), which comprises the steps of adjusting an aqueous solution of an[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt to a temperatureof from 40 to 80° C. and a pH of from 1.9 to 4.5 and then cooling theresulting solution to a temperature below 40° C. over a period of from0.2 to 10 hours while supplying a mineral acid thereto so as to maintainthe pH at from 1.9 to 4.5 to precipitate[S,S]-ethylenediamine-N,N′-disuccinic acid in a high yield; (3) theprocess for obtaining the crystals described in (1), which comprises thesteps of supplying an aqueous solution of an[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt and a mineral acidinto an aqueous solution of an [S,S]-ethylenediamine-N,N′-disuccinicacid metal salt adjusted to a temperature of from 0 to 40° C. and a pHof from 1.9 to 4.5 so as to maintain the pH at from 1.9 to 4.5 and so asto make a residence time from 0.5 to 10 hours, and taking outintermittently or continuously the resulting slurry of[S,S]-ethylenediame-N,N′-disuccinic acid crystals in a high yield; (4)the process described in (2) or (3), wherein the yield of the crystal is90% or more; (5) the process described in (4), in which a cyclization of[S,S]-ethylenediamine-N,N′-disuccinic acid during its crystallization issuppressed; (6) the process described in (2) or (3), wherein the[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt is a sodium saltand/or a magnesium salt; and (7) the process described in (2) or (3),wherein the mineral acid is a sulfuric acid.

BEST MODE FOR CARRYING OUT THE INVENTION

[0010] [S,S]-EDDS contemplated in the present invention is the onehaving a composition that a ratio of [S,S]-isomers to a whole amount ofisomers is 90% by weight or more.

[0011] The term “bulk density” referred to in the present invention isdefined as a value determined according to JIS K5101 for a dry productwith a water content (including crystal water) of 15% by weight or less.

[0012] The term “yield” referred to in the present invention is a valuedetermined by dividing a weight obtained by subtracting a weight of[S,S]-ethylenediamine-N,N′-disuccinic acid disappearing at the time ofcrystallization from a weight of [S,S]-ethylenediamine-N,N′-disuccinicacid present in an aqueous solution of anethylenediamine-N,N′-disuccinic acid salt, by a weight of[S,S]-ethylenediamine-N,N′-disuccinic acid present in the originalaqueous solution, said value being expressed by percent.

[0013] Crystallization can be accomplished, for example, in thefollowing way. In the case of a batch process, an aqueous solution of analkaline metal salt, alkaline earth metal salt or ammonium salt etc. of[S,S]-EDDS with a concentration of from 0.1% by weight to a saturationconcentration, obtained by the above-mentioned enzymatic syntheticmethod from fumaric acid and ethylenediamine (JP-A-9-140390 andEP-A-0805211), is adjusted to a pH in the range of 1.9 to 4.5,preferably 2.5 to 4.0, and a temperature in the range of 40 to 80° C.,preferably 40 to 60° C., and, if necessary after causing a partialprecipitation of [S,S]-EDDS or after adding seed crystals of [S,S]-EDDS,is gradually cooled. Cooling temperature is below 40° C., preferably 30to 10° C., and cooling time, although variable depending on pH andtemperature conditions, is in the range of from 0.2 to 10 hours. In thecase of a continuous process, after adjusting the pH to the range of 1.9to 4.5, preferably 2.4 to 4.0, and the temperature to the range of 0 to40° C., an aqueous solution of an alkaline metal salt, alkaline earthmetal salt or ammonium salt etc. of [S,S]-EDDS is supplied thereto sothat a residence time become 0.5 to 10 hours, preferably 1 to 5 hours,although variable depending on pH and temperature conditions, and theresulting [S,S]-EDDS crystal slurry is taken out continuously orintermittently.

[0014] Although pH rises up gradually with proceeding of acrystallization, pH is adjusted so as to be in a prescribed range byadding an acid as required in this case.

[0015] Such pH adjustment can be usually made by adding a mineral acidsuch as sulfuric acid or hydrochloric acid.

[0016] On the other hand, the lower the pH or the higher the temperatureor the longer the period of time of an exposure to these conditions, theeasier formation of the cyclized products ofethylenediamine-N,N′-disuccinic acid represented by the structuralformulae (1) and (2). The formation of the cyclized product not onlycauses a reduction of a recovery yield of the [S,S]-EDDS crystals butresults in a cause of a reduction of a crystal quality because thecyclized product remaining in a mother liquor adheres to the crystals.However, the use of the above-mentioned preferable conditions cancontrol a less formation of the cyclized product. According to thepresent invention, it is possible to finally obtain the [S,S]-EDDScrystals in a yield of 90% or more.

[0017] Ordinary methods such as filtration, centrifugation, etc., can beemployed for collecting the the precipitated crystals. Then, thecyclized product and sulfates etc. formed in the acid-precipitation ofcrude crystals are washed away with water or an organic solvent. Thiswashing is not subject to any specific restrictions, either, andordinary washing methods such as rinsing and slurry washing etc. can beemployed.

[0018] Drying of wet crystals after washing may be conducted at such atemperature that a temperature of the product be 80° C. or less.

[0019] The present invention is further illustrated by the followingexamples, but it should be understood that the present invention is notrestricted by these examples in any way.

[0020] Methods of analyses and measurements made in the followingExamples are as described below.

[0021] (1) [S,S]-EDDS and its Cyclized Product

[0022] An [S,S]-EDDS solution or a 0.5N sodium hydroxide solution ofcrystals thereof centrifugally sterilized were analyzed by liquidchromatography (column: Inertsil ODS-3; mobile phase: 2 mMtetra-n-butylammonium hydroxide, 2 mM CuSO₄ and 50 mM H₃PO₄; flow rate:1.0 ml/min; temperature: 40° C; detecting wavelength: 220 nm).

[0023] (2) Optical Purity of Ethylenediamine-N,N′-disuccinic Acid

[0024] An [S,S]-EDDS solution or a 0.5N sodium hydroxide solution ofcrystals thereof, in which cells had been centrifugally removed, wereanalyzed by liquid chromatography (column: MCl GEL CRS 10W; mobilephase: 10 mM CUSO₄; flow rate: 0.5 ml/min; temperature: roomtemperature; detecting wavelength: 254 nm).

[0025] (3) Bulk Density

[0026] Bulk density of dry crystals obtained was measured by a bulkdensity measuring instrument mfd. by Tokyo Kuramochi Kaga.ku KikaiSeisakusho Ltd. (JIS K5101).

Production Example 1

[0027] Preparation of [S,S]-EDDS Solution

[0028] Brevundimonas sp. TN-3 strain was cultured to obtain strain cellsaccording to the method described in Example 1 of JP-A-9-140390. ThisTN-3 strain is described in EP-A-0E05211, and it was deposited withNational Institute of Bioscience and Human Technology, Agency ofIndustrial Science and Technology (1-3, Higashi 1-chome, Tsukuba-shi,Ibaraki-ken, Japan) on Apr. 11, 1996, and was afforded InternationalDeposit No. FERM BP-5886 according to Budapest Treaty on theInternational Recognition of the Deposit of Microorganisms for thePurpose of Patent Procedure. The strain cells were suspended in a 100 mMboric acid buffer of pH 9.2 and heat-treated at 45° C. for 8 hours.

[0029] The treated strain cells were collected and then were suspendedin a pH 8.5 reacting solution containing 143 g/l of fumaric acid, 37 g/lof ethylene-diamine and 54 g/l of magnesium hydroxide and reacted withstirring at 40° C. for 3 days while adjusting pH of the reaction mixtureat 8.5 with a sodium hydroxide solution.

[0030] After the reaction was completed, the reaction product solutionwas centrifuged for removing the cells. The obtained supernatantcontained 480 mM [S,S]-EDDS (a ratio of [S,S]-form to whole isomersbeing 98.8% by weight) and completely free of cyclized product of[S,S]-EDDS.

Comparative Example 1

[0031] Sulfuric acid was added to 100 ml of the above [S,S]-EDDSsolution at room temperature (20° C.) to adjust its pH at 1.95. Thesolution was allowed to stand for one hour and precipitated crystalswere filtered by a Buchner funnel and washed with 100 ml of desaltedwater to obtain wet crystals. Drying thereof overnight at 80° C. gaveneedle crystals (0.05-0.2 mm in diameter and 0.5-3 mm length) with abulk density of 0.2 g/cm³ in a yield of 99.5%. Sulfate in the crystalswas 264 ppm, and an amount of cyclized product in a mother liquor wasabout 0.5% based on [S,S]-EDDS supplied.

Comparative Example 2

[0032] To 100 ml of the above [S,S]-EDDS solution heated to 90° C.,sulfuric acid was added to adjust its pH at 3.0. Then the solution wascooled gradually over a period of 2 hours until reaching 30° C., duringwhich period sulfuric acid was gradually added to maintain pH at 3.0.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.6 mm in diameter and1-3 mm length) with a bulk density of 0.6 g/cm³ in a yield of 80%. Anamount of cyclized product in a mother liquor was about 20% based on[S,S]-EDDS supplied.

Comparative Example 3

[0033] To 100 ml of the above [S,S]-EDDS solution heated to 40° C.,sulfuric acid was added to adjust the pH at 3.0, to which the above[S,S]-EDDS solution was further supplied at a rate of 1,000 ml/hr. Inthis operation, a slurry was taken out from time to time so as tomaintain a liquid level at 100 ml (residence time: 0.1 hour). Also,during this period, sulfuric acid was gradually added to maintain the pHat 3.0. Precipitated crystals were filtered by a Buchner funnel andwashed with 100 ml of desalted water to obtain wet crystals. Dryingthereof overnight at 80° C. gave columnar crystals (0.1-0.2 mm indiameter and 0.3-1 mm length) with a bulk density of 0.3 g/cm³ in ayield of 99.5%.

EXAMPLE 1

[0034] To 100 ml of the above [S,S]-EDDS solution heated to 80° C.,sulfuric acid was added to adjust pH at 3.75. Then the solution wascooled gradually over a period of 2 hours until reaching 30° C., duringwhich period sulfuric acid was gradually added so as to maintain pH at3.75. Precipitated crystals were filtered by a Buchner funnel and washedwith 100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.6 mm in diameter and1-3 mm length) with a bulk density of 0.58 g/cm³ in a yield of 91.5%.Sulfate in the crystals was 97 ppm, and an amount of cyclized product ina mother liquor was about 8.5% based on [S,S]-EDDS supplied.

EXAMPLE 2

[0035] To 100 ml of the above [S,S]-EDDS solution heated to 80° C.,sulfuric acid was added to adjust pH at 3.2. Then, the solution wascooled to 60° C. over a period of 30 minutes, maintained at 60° C. forone hour and then again cooled gradually till reaching 21.5° C. over aperiod of one hour. During this period, sulfuric acid was graduallyadded to maintain the pH at 3.2. Precipitated crystals were filtered bya Buchner funnel and washed with 100 ml of desalted water to obtain wetcrystals. Drying thereof overnight at 80° C. gave columnar crystals(0.3-0.6 mm in diameter and 1-3 mm length) with a bulk density of 0.57g/cm³ in a yield of 95.0%. Sulfate content in the crystals was 94 ppm,and an amount of cyclized product in a mother liquor was about 5% basedon [S,S]-EDDS supplied.

EXAMPLE 3

[0036] To 100 ml of the above [S,S]-EDDS solution heated to 60° C.,sulfuric acid was added to adjust pH at 3.2. The solution was maintainedat 60° C. for 30 minutes and then cooled gradually until reaching 21.5°C. over a period of one hour. During this period, sulfuric acid wasgradually added to maintain the pH at 3.2. Precipitated crystals werefiltered by a Buchner funnel and was washed with 100 ml of desaltedwater to obtain wet crystals. Drying thereof overnight at 80° C. gavecolumnar crystals (0.3-0.6 mm in diameter and 1-3 mm length) with a bulkdensity of 0.55 g/cm³ in a yield of 98.0%. Sulfate content in thecrystals was 93 ppm, and an amount of cyclized product in a motherliquor was about 3% based on [S,S]-EDDS supplied.

EXAMPLE 4

[0037] To 100 ml of the above [S,S]-EDDS solution diluted to 3 times andheated to 40° C., sulfuric acid was added to adjust pH at 3.2. Then, thesolution was maintained at 60° C. for 30 minutes and then cooledgradually till reaching 20° C. over a period of one hour. During thisperiod, sulfuric acid was gradually added to maintain the pH at 3.2.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.2-0.7 mm in diameter and1-3.5 mm length) with a bulk density of 0.56 g/cm³ in a yield of 99.5%.Sulfate content in the crystals was 90 ppm, and an amount of cyclizedproduct in a mother liquor was about 0.5% based on [S,S]-EDDS supplied.

EXAMPLE 5

[0038] To 100 ml of the above [S,S]-EDDS solution heated to 40° C.,sulfuric acid was added to adjust pH at 3.0, to which the above[S,S]-EDDS solution was further supplied at a rate of 50 ml/hr. In thisoperation, a slurry was taken out from time to time so as to keep aliquid level at 100 ml (residence time: 2 hours). During this period,sulfuric acid was gradually added to maintain the pH at 3.0.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.7 mm in diameter and0.5-1 mm length) with a bulk density of 0.61 g/cm³ in a yield of 99%.

EXAMPLE 6

[0039] To 100 ml of the above [S,S]-EDDS solution heated to 20° C.,sulfuric acid was added to adjust pH at 3.0, to which the above[S,S]-EDDS solution was further supplied at a rate of 30 ml/hr. In thisoperation, a slurry was taken out from time to time so as to keep aliquid level at 100 ml (residence time: 3.3 hours). During this period,sulfuric acid was gradually added to maintain the pH at 3.0.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.6 mm in diameter and0.4-1 mm length) with a bulk density of 0.58 g/cm³ in a yield of 99.5%.

[0040] Industrial Applicability

[0041] Crystals of [S,S]-EDDS according to the present invention arecolumnar crystals (about 0.3-0.7 mm in diameter and about 0.5-1 mmlength) with a bulk density of 0.45 to 1.2 g/cm³. These crystals are farbetter in washing, drying and transporting efficiencies than needlecrystals (about 0.05-0.2 mm in diameter and about 0.5-3 mm length) witha bulk density of about 0.2 g/cm³ obtained by the conventionalacid-precipitation method in which a mineral acid is added at normaltemperature or under cooling. Also, the [S,S]-EDDS crystals of thepresent invention are substantially free of impurities such as salts andcyclized product of [S,S]-EDDS formed during acid precipitation, henceare high in quality. Further, these crystals can be obtained in a highyield.

1. Crystals of [S,S]-ethylenediamine-N,N′-disuccinic acid which have abulk density of from 0.45 to 1.2 g/cm³.
 2. A process for obtaining thecrystals according to claim 1, comprising the steps of adjusting anaqueous solution of an [S,S] -ethylenediamine-N,N′-disuccinic acid metalsalt to a temperature of from 40 to 80° C. and a-pH of from 1.9 to 4.5,and then cooling the resulting solution to a temperature below 40° C.over a period of from 0.2 to 10 hours while supplying a mineral acidthereto so as to maintain the pH at from 1.9 to 4.5 to precipitate[S,S]-ethylenediamine-N,N′-disuccinic acid in a high yield.
 3. A processfor obtaining the crystals according to claim 1, comprising the steps ofsupplying an aqueous solution of an[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt and a mineral acidinto an aqueous solution of an [S,S]-ethylenediamine-N,N′-disuccinicacid metal salt adjusted to a temperature of from 0 to 40° C. and a pHof from 1.9 to 4.5 so as to maintain the pH at from 1.9 to 4.5 and so asto make a residence time from 0.5 to 10 hours, and taking outintermittently or continu-ously the resulting slurry of[S,S]-ethylenediamine-N,N′-disuccinic acid crystals in a high yield. 4.The process according to claims 2 or 3, wherein the yield of thecrystals is 90% or more.
 5. The process according to claim 4, in which acyclization of [S,S]-ethylenediamine-N,N′-disuccinic acid during itscrystallization is suppressed.
 6. The process according to any one ofclaims 2 to 5, wherein the [S,S]-ethylenediamine-N,N′-disuccinic acidmetal salt is a sodium salt and/or a magnesium salt.
 7. The processaccording to claims 2 or 3, wherein the mineral acid is a sulfuric acid.